Auraptene nanoparticles ameliorate testosterone-induced benign prostatic hyperplasia in rats: Emphasis on antioxidant, anti-inflammatory, proapoptotic and PPARs activation effects
Almukadi, Haifa; Eid, Basma G; Shaik, Rasheed A; Abdel-Naim, Ashraf B; Ahmed Esmat;
Abstract
Benign prostatic hyperplasia (BPH) is a disease that commonly strikes the majority of aged men. Developing new therapies to manage BPH with improved efficacy and safety is strongly needed. In this regard, auraptene is a natural compound with multiple pharmacological effects, but with poor oral bioavailability. This investigation aimed to assess the possible protection offered by auraptene-nanostructured lipid carrier (auraptene-NLC) in a BPH model induced by testosterone in rats. Auraptene-NLC had optimum particle size and drug release profile compared to raw auraptene. At doses (5 and 10 mg/kg), it hampered the rise in prostatic weights & indices relative to rats challenged with testosterone. Moreover, auraptene-NLC alleviated histopathological abnormalities in prostate architecture and decreased the glandular epithelial height. Additionally, testosterone-induced oxidative stress was alleviated by auraptene-NLC and inhibited raised lipid peroxidation, catalase and superoxide dismutase exhaustion as well as enhanced glutathione content. Moreover, it significantly reduced the prostate content of nuclear factor κB, Interleukins1β & 6, as well as transforming growth factor β, compared to testosterone group. The proapoptotic activity of auraptene-NLC (10 mg/kg) was confirmed by a significant increase of prostate cleaved caspase-3, boosted Bax/Bcl2 mRNA ratio that was further confirmed by assessing their protein expressions. Furthermore, the beneficial effects of auraptene-NLC against BPH were substantiated by ameliorating testosterone-induced decline of nuclear PPARα & PPARγ and inhibiting the increased expression of cyclin D1 protein. In conclusion, auraptene-NLC offers a protective effect in rats whereby BPH was induced by testosterone, via its anti-inflammatory, antioxidant and proapoptotic activities, and PPAR family activation.
Other data
Title | Auraptene nanoparticles ameliorate testosterone-induced benign prostatic hyperplasia in rats: Emphasis on antioxidant, anti-inflammatory, proapoptotic and PPARs activation effects | Authors | Almukadi, Haifa; Eid, Basma G; Shaik, Rasheed A; Abdel-Naim, Ashraf B; Ahmed Esmat | Keywords | Auraptene;Benign prostatic hyperplasia;PPAR;Rats | Issue Date | Nov-2021 | Journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Volume | 143 | ISSN | 07533322 | DOI | 10.1016/j.biopha.2021.112199 | PubMed ID | 34649341 | Scopus ID | 2-s2.0-85115798817 |
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